Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2485460 | Journal of Pharmaceutical Sciences | 2013 | 8 Pages |
Abstract
Doxorubicin (DOX) is an anthracycline antibiotic with a broad antitumor spectrum. However, the clinical use of DOX is limited because of its cardiotoxicity, a doseâdependent effect. Colloidal drug delivery systems, such as microemulsions (MEs), allow the incorporation of drugs, modifying the pharmacokinetic (PK) profile and toxic effects. In this study, we evaluated the PK profile and cardiotoxicity of a new DOX ME (DOXâME). The PK profile of DOXâME was determined and compared with that of the conventional DOX after singleâdose administration (6âmg/kg, intravenous) in male Wistar rats (n = 12 per group). The cardiotoxicity of DOX formulations was evaluated by serum creatine kinase MB (CKMB) activity in both animal groups before and after drug administration. The plasma DOX measurements were performed by highâperformance liquid chromatography with fluorescence detection, and the CKMB levels were assayed using the CKMB Labtest® kit. The ME system showed a significant increase in plasma DOX concentrations and lower distribution volume when compared with conventional DOX. Serum CKMB activity increased after conventional DOX administration but was unchanged in the DOXâME group. These results demonstrate modifications in drug access to susceptible sites using DOXâME. DOXâME displayed features that make it a promising system for future therapeutic application.
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Authors
Juliana Uruguay Correa Vidigal AssumpçãO, Michel Leandro Campos, Marco Antonio Ferraz Nogueira Filho, Kelly Chrystina Pestana, Helen Mariana Baldan, Thalita Pedroni Formariz Pilon, Anselmoc Gomes de Oliveira, Rosângela Gonçalves Peccinini,